Copyright (c) 2025 Disha Dhabarde
This work is licensed under a Creative Commons Attribution 4.0 International License.
Design, Synthesis, Characterization and Molecular Docking Studies of Some Pyrrolotriazine containing 1H-Pyrazole Derivatives as Anticancer Agent Against Breast Cancer
Corresponding Author(s) : Disha M. Dhabarde
Asian Journal of Chemistry,
Vol. 37 No. 12 (2025): Vol 37 Issue 12, 2025
Abstract
Pyrrolotriazine containing 1(H)pyrazole and its derivatives were designed, synthesized and screened for anticancer activity. Novel pyrazole derivatives incorporating a pyrrolotriazine moiety were rationally designed and synthesized via the Claisen-Schmidt condensation pathway. Initially, pyrrolotriazine was obtained through the condensation of pyrrole-2-carbaldehyde with hydroxylamine. Subsequent acetylation with acetyl chloride yielded acetylpyrrolotriazine, which was then condensed with various substituted benzaldehydes to afford pyrrolotriazine-based chalcones. These chalcone intermediates, upon cyclization with hydrazine hydrate, produced the target pyrazole-containing pyrrolotriazine derivatives. The synthesized compounds were characterized by spectroscopic techniques and evaluated for their potential anticancer activity against breast cancer cell lines. Docking study of synthesized compounds (R1-15) were performed by using PDB ID 8DUG with docking score of -10.5 Kcal/mol. Among the designed compounds, pyrazole derivatives (R1-15) exhibiting the highest binding affinities were synthesized and characterized using various spectroscopic techniques. Anticancer activity of synthesized compounds was evaluated against the human breast cancer cell line MCF-7, compounds R1, R2 and R13 showed significant cytotoxic activity. Among this 4-fluoro substituent possess highest anti-breast cancer activity due to lipohilicity, membrane permeability and balance between electronic and steric effect, hence suggested that the synthesized compounds would be useful as anticancer drugs.
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A.A. Abbas, T.A. Farghaly and K.M. Dawood, RSC Adv., 14, 19752 (2024); https://doi.org/10.1039/D4RA01387E
D. Kumar and S.K. Jain, Curr. Med. Chem., 23, 4338 (2016); https://doi.org/10.2174/0929867323666160809093930
M.H.A. Al-Jumaili, E.A. Bakr, M.A. Huessien, A.S. Hamed and M. J. Muhaidi, Heterocycl. Commun., 31, 20220179 (2025); https://doi.org/10.1515/hc-2022-0179
A. Omar, Al-Azhar J. Pharm. Sci., 62, 39 (2020); https://doi.org/10.21608/ajps.2020.118375
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J. Yayan, K.-J. Franke, M. Berger, W. Windisch and K. Rasche, Mol. Biol. Rep., 51, 165 (2024); https://doi.org/10.1007/s11033-023-08920-5
J. Ferlay, M. Colombet, I. Soerjomataram, C. Mathers, D.M. Parkin, M. Piñeros, A. Znaor and F. Bray, Int. J. Cancer, 144, 1941 (2019); https://doi.org/10.1002/ijc.31937
W. Liu, J. Fang, M. Zhu, J. Zhou and C. Yuan, BMC Pediatr., 25, 571 (2025); https://doi.org/10.1186/s12887-025-05847-7
R.L. Siegel, A.N. Giaquinto and A. Jemal, CA Cancer J. Clin., 74, 12 (2024); https://doi.org/10.3322/caac.21820
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A. Daina, O. Michielin, and V. Zoete, Sci. Rep., 7, 42717 (2017); https://doi.org/10.1038/srep42717
D.E.V. Pires, T.L. Blundell, and D.B. Ascher, J. Med. Chem., 58, 4066 (2015); https://doi.org/10.1021/acs.jmedchem.5b00104
C.A. Lipinski, F. Lombardo, B.W. Dominy and P.J. Feeney, Adv. Drug Delivery Rev., 23, 3 (1997); https://doi.org/10.1016/S0169-409X(96)00423-1
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